| IED ID | IndEnz0010000780 |
| Enzyme Type ID | esterase000780 |
| Protein Name |
Lipoprotein lipase LPL EC 3.1.1.34 Phospholipase A1 EC 3.1.1.32 |
| Gene Name | LPL LIPD |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MESKALLVLTLAVWLQSLTASRGGVAAADQRRDFIDIESKFALRTPEDTAEDTCHLIPGVAESVATCHFNHSSKTFMVIHGWTVTGMYESWVPKLVAALYKREPDSNVIVVDWLSRAQEHYPVSAGYTKLVGQDVARFINWMEEEFNYPLDNVHLLGYSLGAHAAGIAGSLTNKKVNRITGLDPAGPNFEYAEAPSRLSPDDADFVDVLHTFTRGSPGRSIGIQKPVGHVDIYPNGGTFQPGCNIGEAIRVIAERGLGDVDQLVKCSHERSIHLFIDSLLNEENPSKAYRCSSKEAFEKGLCLSCRKNRCNNLGYEINKVRAKRSSKMYLKTRSQMPYKVFHYQVKIHFSGTESETHTNQAFEISLYGTVAESENIPFTLPEVSTNKTYSFLIYTEVDIGELLMLKLKWKSDSYFSWSDWWSSPGFAIQKIRVKAGETQKKVIFCSREKVSHLQKGKAPAVFVKCHDKSLNKKSG |
| Enzyme Length | 475 |
| Uniprot Accession Number | P06858 |
| Absorption | |
| Active Site | ACT_SITE 159; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:1371284, ECO:0000269|PubMed:30559189"; ACT_SITE 183; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:1371284, ECO:0000305|PubMed:30559189"; ACT_SITE 268; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:1371284, ECO:0000305|PubMed:30559189" |
| Activity Regulation | ACTIVITY REGULATION: The apolipoprotein APOC2 acts as a coactivator of LPL activity (PubMed:12032167). Ca(2+) binding promotes protein stability and formation of the active homodimer (PubMed:16179346). Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4 (PubMed:27929370, PubMed:29899144). Inhibited by NaCl (PubMed:12032167). {ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:16179346, ECO:0000269|PubMed:27929370, ECO:0000269|PubMed:29899144}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.34; Evidence={ECO:0000269|PubMed:11342582, ECO:0000269|PubMed:11893776, ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:1371284, ECO:0000269|PubMed:16179346, ECO:0000269|PubMed:2340307, ECO:0000269|PubMed:26725083, ECO:0000269|PubMed:27578112, ECO:0000269|PubMed:29899144, ECO:0000269|PubMed:30559189, ECO:0000269|PubMed:7592706}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:18689, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:57643, ChEBI:CHEBI:57875; EC=3.1.1.32; Evidence={ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:7592706}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + di-(9Z)-octadecenoylglycerol + H(+); Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945; Evidence={ECO:0000269|PubMed:12032167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576; Evidence={ECO:0000305|PubMed:12032167}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:38699, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:74669, ChEBI:CHEBI:76083; Evidence={ECO:0000269|PubMed:7592706};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38700; Evidence={ECO:0000305|PubMed:7592706}; CATALYTIC ACTIVITY: Reaction=1,2,3-tributanoylglycerol + H2O = butanoate + dibutanoylglycerol + H(+); Xref=Rhea:RHEA:40475, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:35020, ChEBI:CHEBI:76478; Evidence={ECO:0000269|PubMed:7592706};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40476; Evidence={ECO:0000305|PubMed:7592706}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) + hexadecanoate + hexadecanoyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:41384, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64563, ChEBI:CHEBI:72999; Evidence={ECO:0000269|PubMed:12032167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41385; Evidence={ECO:0000305|PubMed:12032167}; |
| DNA Binding | |
| EC Number | 3.1.1.34; 3.1.1.32 |
| Enzyme Function | FUNCTION: Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage (PubMed:8675619, PubMed:11342582, PubMed:27578112). Although it has both phospholipase and triglyceride lipase activities it is primarily a triglyceride lipase with low but detectable phospholipase activity (PubMed:7592706, PubMed:12032167). Mediates margination of triglyceride-rich lipoprotein particles in capillaries (PubMed:24726386). Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans (PubMed:11342582, PubMed:27811232). {ECO:0000269|PubMed:11342582, ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:24726386, ECO:0000269|PubMed:27578112, ECO:0000269|PubMed:27811232, ECO:0000269|PubMed:7592706, ECO:0000269|PubMed:8675619}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (26); Chain (1); Disulfide bond (5); Domain (1); Glycosylation (2); Helix (14); Metal binding (4); Modified residue (3); Mutagenesis (17); Natural variant (75); Region (5); Signal peptide (1); Turn (5) |
| Keywords | 3D-structure;Calcium;Cell membrane;Chylomicron;Direct protein sequencing;Disease variant;Disulfide bond;Extracellular matrix;Glycoprotein;Heparin-binding;Hydrolase;Hyperlipidemia;Lipid degradation;Lipid metabolism;Membrane;Metal-binding;Nitration;Reference proteome;Secreted;Signal;VLDL |
| Interact With | Q8TAB7; Q9UI10; Q8IV16; O00746; C9J082; O14744; Q8TAS3; O00233; Q8IYM2; Q9UMY4; O43493-5; Q8NFB2; Q8N0U8 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P11151}; Peripheral membrane protein {ECO:0000250|UniProtKB:P11151}; Extracellular side {ECO:0000250|UniProtKB:P11151}. Secreted {ECO:0000269|PubMed:11342582, ECO:0000269|PubMed:11893776, ECO:0000269|PubMed:12641539, ECO:0000269|PubMed:1371284, ECO:0000269|PubMed:2340307, ECO:0000269|PubMed:27578112, ECO:0000269|PubMed:30559189}. Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:27811232}. Note=Newly synthesized LPL binds to cell surface heparan proteoglycans and is then released by heparanase. Subsequently, it becomes attached to heparan proteoglycan on endothelial cells (PubMed:27811232). Locates to the plasma membrane of microvilli of hepatocytes with triglyceride-rich lipoproteins (TRL). Some of the bound LPL is then internalized and located inside non-coated endocytic vesicles (By similarity). {ECO:0000250|UniProtKB:P11151, ECO:0000269|PubMed:27811232}. |
| Modified Residue | MOD_RES 121; /note=3'-nitrotyrosine; /evidence=ECO:0000250|UniProtKB:Q06000; MOD_RES 191; /note=3'-nitrotyrosine; /evidence=ECO:0000250|UniProtKB:Q06000; MOD_RES 343; /note=3'-nitrotyrosine; /evidence=ECO:0000250|UniProtKB:Q06000 |
| Post Translational Modification | PTM: Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity. {ECO:0000250|UniProtKB:Q06000}. |
| Signal Peptide | SIGNAL 1..27; /evidence=ECO:0000269|PubMed:2340307 |
| Structure 3D | X-ray crystallography (5) |
| Cross Reference PDB | 6E7K; 6OAU; 6OAZ; 6OB0; 6WN4; |
| Mapped Pubmed ID | 10085125; 10091829; 10206232; 10364086; 10636447; 10723106; 10830909; 10900462; 10936883; 10974229; 11018310; 11071388; 11073182; 11096142; 11126401; 11132601; 11140837; 11171287; 11194013; 11205691; 11229437; 11284423; 11316129; 11341749; 11395037; 11427211; 11441189; 11484171; 11500192; 11533368; 11534394; 11571596; 11593500; 11605530; 11680797; 11683775; 11702052; 11702219; 11711487; 11714857; 11714860; 11730816; 11796707; 11852057; 11893778; 11897170; 11899831; 11921083; 11947965; 11996946; 12042669; 12044583; 12082592; 12107736; 12117735; 12133533; 12133567; 12164879; 12174215; 12208477; 12226739; 12230584; 12370850; 12408999; 12409958; 12446192; 12483461; 12501246; 12514935; 12544508; 12573449; 12636935; 12647273; 12655575; 12679477; 12687649; 12690214; 12704407; 12708905; 12732844; 12740382; 12746411; 12747600; 12777470; 12782148; 1279089; 12793009; 12818414; 12862202; 12865761; 12866915; 12876415; 12889841; 12905705; 12915220; 12919138; 12964943; 14553962; 14564687; 14570890; 14580156; 14580165; 14581156; 14669227; 14693718; 14764824; 14967813; 14984315; 14988233; 14988305; 15019539; 15051515; 15060087; 15076187; 15115692; 15127290; 15135251; 15155715; 15178420; 15189363; 15202783; 15221136; 15253101; 15256516; 15257172; 15270617; 15292370; 15292372; 15331147; 15356086; 15386377; 15543643; 15545743; 15562208; 15608561; 15637076; 15657615; 15696473; 15699916; 15721013; 15749185; 15764642; 15793775; 15795426; 15802535; 15857159; 15858619; 15878772; 15896905; 15928243; 15939061; 15961789; 15979432; 15994321; 16015281; 16029634; 16030523; 16086925; 16106048; 16109723; 16122151; 16132104; 16135440; 16141008; 16142021; 16168296; 16169070; 16195478; 16200213; 16205020; 16253639; 16256241; 16343038; 16353345; 16357806; 16364275; 16369102; 16378107; 16380219; 16416313; 16418216; 16419488; 16430904; 16431216; 16449872; 16451134; 16460718; 16466345; 16517593; 16519597; 16534528; 16542392; 16544732; 16552397; 16630553; 16635607; 16651467; 16702309; 16741292; 16755277; 16763159; 16770077; 16776623; 16799404; 16813599; 16822320; 16829344; 16837242; 16840197; 16864937; 16894468; 16926441; 16928730; 16965549; 16989840; 17001213; 17006673; 17029199; 17032721; 17058522; 17072956; 17088546; 17093291; 17130180; 17137217; 17157861; 17163816; 17244606; 17291198; 17299085; 17299379; 17311894; 17318300; 17328917; 17342071; 17347923; 17356047; 17374417; 17428620; 17436307; 17463246; 17473385; 17476032; 17484619; 17487735; 17517063; 17533471; 17535427; 17555736; 17560523; 17562973; 17568951; 17587400; 17615573; 17620184; 17644777; 17652898; 17653444; 17662793; 17681919; 17700364; 17705673; 17706445; 17717288; 17721767; 17726453; 17727701; 17761930; 17803213; 17848837; 17855807; 17883852; 17903299; 17919884; 17939375; 18020971; 18068174; 18175800; 18187430; 18193043; 18193044; 18193046; 18223635; 18242618; 18275685; 18275964; 18321693; 18325076; 18336668; 18354102; 18449420; 18454146; 18494281; 18513389; 18534873; 18535540; 18590804; 18596051; 18603820; 18616755; 18619685; 18635818; 18636124; 18649389; 18660489; 18676680; 18681781; 18693040; 18724972; 18821565; 18823627; 18922999; 18927546; 18985010; 18986377; 18996102; 19004026; 19018513; 19028676; 19034041; 19034316; 19052449; 19060906; 19060910; 19060911; 19099922; 19131662; 19148283; 19155782; 19167106; 19170196; 19185650; 19191728; 19207029; 19246456; 19254215; 19259048; 19295657; 19304573; 19318355; 19335919; 19336370; 19336475; 19340428; 19357293; 19367093; 19367320; 19368142; 19403283; 19420105; 19428034; 19471043; 19479237; 19489872; 19501493; 19534808; 19542565; 19556723; 19558660; 19563912; 19578796; 19584682; 19596235; 19602472; 19625176; 19629056; 19642912; 19656773; 19664517; 19689828; 19692168; 19709746; 19729601; 19766899; 19772655; 19773416; 19780863; 19818126; 19834535; 19875996; 19878569; 19884647; 19888660; 19899640; 19910634; 19913121; 19948975; 19956635; 20031538; 20031551; 20031591; 20075597; 20092038; 20099167; 20124439; 20150529; 20160193; 20167577; 20228263; 20235787; 20347446; 20350420; 20385819; 20400780; 20403997; 20410100; 20416077; 20421589; 20429872; 20430250; 20430392; 20452482; 20506644; 20536507; 20538960; 20565774; 20571754; 20581395; 20588308; 20596061; 20602615; 20616609; 20628086; 20634891; 20650961; 20657596; 20673868; 20679960; 20691829; 20693566; 20694148; 20712903; 20714348; 20836743; 20855565; 20864672; 20926921; 20943490; 21044743; 21060192; 21127884; 21146168; 21159338; 21162862; 21193198; 21252727; 21398697; 21419757; 21448664; 21478160; 21499891; 21508119; 21518912; 21621348; 21722517; 21816453; 21840003; 21844202; 21854610; 21862952; 21943158; 21966368; 21978733; 21980507; 21988832; 22018640; 22078753; 22095987; 22123668; 22239554; 22244040; 22368174; 22541364; 22729917; 22740495; 22772754; 22773878; 22810051; 22820186; 22828442; 22837712; 23008484; 23020258; 23056264; 23089926; 23320821; 23344322; 23377670; 23478142; 23614796; 23623643; 23661675; 23735640; 23761384; 23880163; 23991054; 24004859; 24009459; 24039871; 24081181; 24121499; 24205968; 24212298; 24223199; 24308220; 24314358; 24340925; 24397894; 24400599; 24407533; 24458708; 24462462; 24591733; 24646025; 24704550; 24704626; 24762672; 24793350; 24847699; 24886709; 24905278; 24988117; 24990426; 25073452; 25131724; 25149060; 25156894; 25239670; 25387803; 25445417; 25554608; 25566792; 25579610; 25589507; 25595992; 25597500; 25626708; 25784555; 25809647; 25811490; 25897955; 25948680; 25966443; 25995285; 26025183; 26026161; 26101956; 26214456; 26342331; 26370976; 26388538; 26420199; 26503844; 26558352; 26589911; 26820803; 26853140; 26933753; 26934567; 26934667; 26975783; 26999119; 27040450; 27055971; 27114411; 27159952; 27185377; 27206937; 27270932; 27400425; 27412455; 27415775; 27494936; 27573733; 27676127; 27757836; 27845686; 27864281; 27875259; 27908779; 27984852; 28126606; 28143480; 28267856; 28275220; 28293042; 28327359; 28397436; 28476858; 28502159; 28502509; 28640651; 28687421; 28689531; 28694296; 28777751; 28916403; 29153744; 29175215; 29206143; 29288010; 29303250; 29438437; 29517609; 29555209; 29615667; 29626981; 29687697; 29718838; 30685441; 30694319; 30932419; 30944368; 31072929; 31208038; 31323462; 31519763; 31543446; 31599081; 31619059; 31645434; 31740790; 31769250; 31923423; 32034094; 32264896; 32333632; 32430061; 32690595; 32833105; 32886944; 33003532; 33239171; 33361851; 33482195; 33526736; 34152845; 34311079; 34324844; 34356640; 34591432; 34780727; 35052431; 3942763; 5057882; 7592670; 7905375; 8020465; 8102341; 8724108; 8728311; 9026529; 9102182; 9120004; 9136889; 9181356; 9264476; 9351361; 9387400; 9404225; 9489234; 9550358; 9555857; 9678774; |
| Motif | |
| Gene Encoded By | |
| Mass | 53,162 |
| Kinetics | |
| Metal Binding | METAL 194; /note=Calcium; via carbonyl oxygen; /evidence=ECO:0000305|PubMed:30559189; METAL 197; /note=Calcium; via carbonyl oxygen; /evidence=ECO:0000305|PubMed:30559189; METAL 199; /note=Calcium; via carbonyl oxygen; /evidence=ECO:0000305|PubMed:30559189; METAL 202; /note=Calcium; /evidence=ECO:0000305|PubMed:30559189 |
| Rhea ID | RHEA:12044; RHEA:18689; RHEA:38575; RHEA:38576; RHEA:38699; RHEA:38700; RHEA:40475; RHEA:40476; RHEA:41384; RHEA:41385 |
| Cross Reference Brenda | 3.1.1.34; |